Reduced high harmonic power spectra in patients with old myocardial infarction

Acceleration of blood flow ejected from the ventricle into the aorta and the hydraulic power state of blood flow in the aorta may be affected by asynchronous or locally depressed contraction of the left ventricle as well as by arterial impedance. In order to evaluate the effect of an infarcted heart on the hydraulic power state of blood flow, the aortic input impedance spectrum and the hydraulic power spectrum were calculated from simultaneous recordings of pulsatile aortic pressure and flow velocity at the aortic root in 6 normal controls (group 1), 6 patients with old myocardial infarction (OMI) without aneurysm (group 2), and 6 patients of OMI with aneurysm (group 3). The ratios (Rh) of power in high harmonics to that of fundamental harmonics, that is, Rh = (E2 + E3 + ...E10)/E1, where E represents hydraulic power and the numbers represent harmonic numbers, were 0.64 +/- 0.17, 0.23 +/- 0.09, and 0.22 +/- 0.10 in groups 1, 2, and respectively (p less than 0.001 between groups 1 and 2; p less than 0.001, between groups 1 and 3). As the acceleration of ejecting flow of blood by the left ventricle is inversely related with arterial impedance, Rh will be also inversely related with arterial impedance. Then, the product of Rh and the characteristic impedance (Zc) would be an indicator of the left ventricular contractility. In fact, the products were 64 +/- 15, 32 +/- 14, and 31 +/- 13 dyne.sec.cm-5 in groups 1, 2, and 3 respectively (p less than 0.005, between groups 1 and 2; p less than 0.005, between groups 1 and 3). These results suggest that asynchronous or locally depressed contractions of the left ventricular wall are closely related to depressed Rh and further to depressed values of the products of Rh and Zc. It is concluded that analysis of the power spectrum of blood flow in the root of the aorta provides information of the left ventricular contractility in connection with arterial impedance.     

Interleukin-1β measurement in stimulated whole blood cultures is useful to predict response to anti-TNF therapies in rheumatoid arthritis

Objective. In RA, response to TNF blockers may be associated with a profile of cytokine production unique to each patient. This study sought to predict the response to biologic agents by examining pro-inflammatory cytokine synthesis in stimulated whole blood cultures (WBCs). Methods. We measured the concentration of TNF-α, IL-1β and IL-6 in supernatants of lipopolysaccharide (LPS)-stimulated WBCs obtained from RA patients (n?=?41) before anti-TNF therapy (infliximab, 13; etanercept, 26; and adalimumab, 2) and from healthy controls (n?=?12). At 24 weeks after biologics, whole bloods were again drawn from 14 of 41 patients. Response was defined by the European League Against Rheumatism response criteria after 24 weeks of therapy. Results. Among 41 patients, 32 were responders (good 14/moderate 18), while 9 were non-responders. All cytokines measured were significantly lower in RA patients than in controls. In RA, IL-1β production was lower in non-responders than in responders [median (interquartile range): 3.5 (1.5-9.4) vs 10.0 (5.1-93.1) pg/ml, P?=?0.048]. The area under the curve from a receiver operating characteristic curve analysis for the prediction of response using IL-1β was 0.717 (95% CI 0.520, 0.914). The sensitivity and specificity of IL-1β (cut-off value 4.84?pg/ml) was 78.1 and 77.8%, respectively. All cytokines were significantly higher 6 months later compared with their respective baseline. Conclusion. IL-1β measurement in LPS-stimulated WBC is useful to predict responsiveness to anti-TNF agents. Cytokine production capacities in LPS-stimulated WBCs are up-regulated by biologics.     

Multifunctional,self-assembling anionic peptide-lipid nanocomplexes for targeted siRNA delivery

Formulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated liposomes and cationic targeting peptides that overcome these problems. Biophysical measurements indicated that at optimal ratios of components, anionic PEGylated nanocomplexes formed spherical particles and that, unlike cationic nanocomplexes, were resistant to aggregation in the presence of serum, and achieved significant gene silencing although their non-PEGylated anionic counterparts were less efficient. We have evaluated the utility of anionic nanoparticles for the treatment of neuronal diseases by administration to rat brains of siRNA to BACE1, a key enzyme involved in the formation of amyloid plaques. Silencing of BACE1 was achieved in vivo following a single injection of anionic nanoparticles by convection enhanced delivery and specificity of RNA interference verified by 5′ RACE-PCR and Western blot analysis of protein.     

Functional dissociation between Kana and Kanji: agraphia following a thalamic hemorrhage

We report the case of a 61-year-old woman with a left thalamic hemorrhage causing agraphia of Kanji (morphograms). Single-photon emission computed tomography (SPECT) showed a decrease in the blood flow in the left thalamus from the superior temporal convolution to the parietal lobe, as well as in the frontal lobe while computed tomography showed no remarkable lesions in the cortex. The agraphia in this case may be due to the thalamic lesion itself, but the SPECT findings strongly suggest that a secondary cortical lesion may be involved in producing the higher cognitive disorder.     

Quantitative assessment of impairment in constructional ability by cube copying in patients with aphasia

Constructional apraxia was evaluated in patients with aphasia using a cube-copying task. It was assessed whether quantitative assessment of cube copying could be used to estimate the performance intelligence quotient (IQ) according to neuropsychological tests. Abnormality in the cube-copying test was observed in 42 of 46 patients (91.3%). Performance according to Raven's coloured progressive matrices and the revised Wechshler adult intelligence scale (WAIS-R) in patients with poor cube copying was significantly lower than in the other four patients. Numbers of the connections completed and plane-orientation errors made in the cube-copying test were significantly correlated with performance IQ on the WAIS-R, correlating particularly with block design, digit symbol, and object assembly in performance IQ subtests. The quantitatively scored cube-copying test, then, can roughly predict non-verbal IQ in patients with aphasia.     

Activin A: an autocrine regulator of cell growth and differentiation in renal proximal tubular cells

BACKGROUND: Activin A is involved in tubular regeneration after ischemia/reperfusion injury. The present study was conducted to examine the role of activin A in cell growth, apoptosis and differentiation of tubular cells. METHODS: We performed cell proliferation assays (MTT assay, [3H]-thymidine incorporation) and apoptosis detection assays (nuclear staining, DNA ladder formation, TUNEL staining) using LLC-PK1 cells. Expression of activin and activin receptor in LLC-PK1 cells also were examined by real-time polymerase chain reaction (PCR) and immunostaining. Stable cell lines expressing the truncated type II activin receptor were generated and the phenotype of these cells was analyzed. RESULTS: Activin A inhibited DNA synthesis and cell growth in a dose-dependent manner and induced apoptosis in LLC-PK1 cells. The expression level of mRNA for the activin betaA subunit was markedly increased when the growth was stimulated. The expression of the type II activin receptor was observed in LLC-PK1 cells. The growth rate of cells expressing dominantly negative activin receptor was significantly faster than that of non-transfected cells. The expression level and pattern of cytokeratin and vimentin in these cells were quite different compared to non-transfected cells. When cultured in collagen gel, these cells formed multiple processes, which was not observed in non-transfected cells. Finally, the expression of Pax-2 was markedly elevated in these cells. CONCLUSIONS: Activin A acts as an autocrine inhibitor of cell growth, an inducer of apoptosis, and an important modulator of differentiation in cultured proximal tubular cells.     

Effect of environmental changes on oxidative deoxyribonucleic acid (DNA) damage in systemic lupus erythematosus

In a study conducted in Japan, the authors used urinary 8-hydroxydeoxyguanosine (8-OHdG) to study the effects of high-intensity and low-intensity sunlight on oxidative damage to deoxyribonucleic acid (DNA) in patients who had systemic lupus erythematosus (SLE). During late May through early September (i.e., a period of high-intensity sunlight), the mean urinary 8-OHdG level in SLE patients was significantly higher than in controls (31.0 +/- 20.6 [standard deviation] ng/mg vs. 15.4 +/- 7.2 ng/mg, respectively [p < .05]). During late November through early March (i.e., low-intensity sunlight season), however, no significant differences were noted (15.4 +/- 5.5 ng/mg vs. 16.3 +/- 4.6 ng/mg, respectively). The mean urinary 8-OHdG level in SLE patients during the period of high-intensity sunlight was significantly higher than during the period of low-intensity sunlight (21.3 +/- 20.6 ng/mg vs. 12.6 +/- 6.7 ng/mg, respectively; p < .01), although no such seasonal changes were observed among controls (16.2 +/- 8.0 ng/mg vs. 15.7 +/- 5.1 ng/mg, respectively). The effect of sunlight intensity (i.e., season) may require consideration when oxidative DNA damage occurs in individuals who have SLE.